BASIC CONSIDERATIONS

Embryology: Fetal kidneys initially develop in pelvic region from 5th week onwards, before ascending cephalad to lumbar region. Kidneys develop from intermediate mesoderm lying between the paraxial and lateral plate mesoderm on posterior abdominal wall of embryo, via two modes: (a) the collecting system develops from the ureteric bud, i.e.

While anatomical nephrogenesis is incomplete till 36 weeks of gestation, urine excretion begins from 10th week onwards, contributing to the amniotic fluid. Presence of oligohydramnios is an important indicator of severe or bilateral renal/urinary tract malformations. Anatomy: Kidneys are paired, bean-shaped organs, located retroperitoneally in lumbar (L1-4) paravertebral space, right being slightly lower than left kidney. Normal kidney measures ~6 cm and ~24 gm in term newborns and ~12 cm and ~150 gm in adults. Kidneys are relatively protected from trauma due to the location and presence of retroperitoneal fat.

Mature kidneys may be divided into an outer paler layer, i.e. cortex and an inner darker layer, i.e. medulla. Medulla contains 8-12 conical masses pointing towards renal pelvis, i.e. pyramids, while cortical tissue that extends between these pyramids forms the columns of Bertini (Fig. 21.1).

Nephrons: Each kidney contains nearly one million nephrons-the functional unit of excretory system. After birth, numbers of nephrons in each kidney remain

Varsha D Phadke, Apurva Shah, Neha Pandey, Mukesh Agrawal

Fig. 21.1: Renal anatomy.

fixed throughout the life and diseased nephrons are replaced only by scarring, leading to irreversible renal insufficiency.

Each nephron may be divided into two poles- (a) vascular pole or glomerulus for hemofiltration, and (b) urinary pole or renal tubules for transport of glomerular filtrate to collecting system, simultaneously modifying it by complex processes of reabsorption and secretion of water and electrolytes.

Glomerulus is a highly specialized tuft of capillaries (vascular pole), invaginated into a dilated cup-shaped proximal end of renal tubule, i.e. Bowman's capsule (urinary pole). The space between glomeruli and Bowman's capsule is filled with mesangium-composed of mesangial cells and amorphous matrix, which serves as a supporting structure to capillaries.

Vascular and urinary pole of nephrons are separated from each other by:

• Innermost fenestrated endothelial lining of capillaries that acts as a mechanical filter and does not allow particles of gt; 110 A° size to pass.

• Glomerular basement membrane (GBM) between capillary endothelium and mesangial cells on inner side and epithelial cells on outer side

• Outer-most visceral epithelial cells of Bowman's capsule with foot processes.

GBM and visceral epithelial layers are in direct continuation with basement membrane and parietal epithelium of Bowman's capsule, respectively.

All these three layers bear a negative electric charge due to presence of a polyionic surface glycoprotein (podo- calyxin) and sialic acid, which prevents the filtration of negatively-charged plasma ions, e.g. proteins, by 'same­charge-repulsion'.

Renal tubules are structurally and functionally divisible into proximal convoluted tubules (PCT), loop of Henle, distal convoluted tubules (DCT) and collecting ducts. Collecting ducts ultimately open on a papilla at the apical side of pyramids, to drain the fully formed urine into renal calyces (collecting system)

While glomeruli, PCT, DCT and major portion of collecting ducts are present in renal cortex, the medulla contains ascending and descending arms with loop of Henle, vasa recta and terminal parts of collecting ducts. Vascular supply is drawn from ipsilateral renal arteries, which sequentially divide into segmental arteries gt; interlobar arteries gt; arcuate arteries and gt; interlobular arteries — the last one feeding afferent arterioles for glomeruli. Efferent arterioles leave from glomeruli and form an extensive network of peritubular capillaries in cortex, essential for tubular reabsorption, secretion and urinary concentration, before emptying into interlobular veins.

Juxtaglomerular apparatus: The ascending part of the distal tubule in medulla that comes in contact with the afferent arteriole of its own glomeruli, contains more dense cells (macula densa). Macula densa, adjoining afferent arterioles and lacis cells located in between, form the juxaglomerular apparatus, which is involved in renin production and electrolyte homeostasis. Renin is a proteolytic enzyme that converts inactive Angiotensin I to active Angiotensin II-a potent vasoconstrictor.

Physiology: Kidneys are primarily involved in:

(a) excretion of metabolic wastes and toxic products,

(b) regulation of plasma osmolality, electrolytes and acid­base balance, (c) regulation of blood pressure, and (d) other metabolic functions, e.g. renin and erythropoietin production and vitamin D metabolism.

Excretory renal functions may be divided into two components: (a) glomerular filtration, and (b) tubular modification, i.e. reabsorption or secretion.

1. Glomerular filtration mainly depends upon the net result of two opposing forces-capillary hydrostatic pressure (facilitating filtration) and plasma oncotic pressure (opposing filtration), apart from the capillary permeability and glomerular blood flow. Quantitatively, ~20% of glomerular flow is filtered during each passage, with normal glomerular filtration rate (GFR) in adults being ~120 ml/min/1.73 m². Qualitatively, nearly all blood components are filtered except cells (due to large size) and high molecular weight proteins (due to large size and negative charge).

2. Tubular modification: This glomerular filtrate is concentrated and modified in composition according to body needs, during its tubular passage to prevent loss of useful substances, e.g. water and electrolytes (tubular reabsorption) and to excrete harmful metabolites (tubular secretion) in urine.

• Urinary concentration/dilution: Freely filtered from glomeruli, ~99% of water in glomerular filtrate is reabsorbed during tubular flow to maintain nor­mal serum osmolality (280-290 mOsm/kg). While ~ 80% of water is absorbed passively in PCT and descending loop of Henle, remaining ~19% is absorbed in collecting ducts under the control of antidiuretic hormone (ADH). Ascending loop of Henle and DCT are impermeable for water. Extent of water reabsorption depends on many factors, e.g. intravascular blood volume and solute load.

• Acidification of urine is essential to maintain acid­base balance, achieved by reabsorption of filtered bicarbonates (to maintain plasma levels at ~22-24 mEq/L) and secretion of excess H⁺ ions (Ch 7.6).

• Electrolyte modifications: Kidney is major regulator of normal electrolyte balance by increasing or decreasing their urinary excretion, controlled by various hormones and blood levels.

- Sodium reabsorption is closely related to ECF volume. Nearly 99% of filtered Na⁺ is reabsorbed actively-65% in PCT (depends upon the amount filtered), 25% in ascending loop of Henle (along with active chloride transport) and rest in DCT and collecting tubules (aldosterone-mediated).

- Potassium is reabsorbed as well as filtered in tubules. Almost all of the filtered potassium is reabsorbed in PCT and whatever is excreted in urine, is actually derived from secretion in DCT and collecting ducts, in exchange to normalize pH and Na⁺ concentration of ECF.

- Calcium and phosphate excretions are interlinked and mainly depend on paratharmone levels. About 98% of filtered calcium is reabsorbed, mainly in PCT (65%), facilitated by parathormone. Most of the filtered phosphates are also reabsorbed here, though inhibited by parathormone.

• Other substances like glucose and amino acids are actively reabsorbed through specific transport systems, usually linked to sodium transport. As these systems have an upper limit for reabsorption/ secretion (tubular maxim or Tm), a substance load exceeding its Tm leads to its urinary excretion.

Developmental Immaturities in Newborn

About 95% of newborns void urine within 48 hours of birth.

Important developmental handicaps in newborns include:

• Lower GFR (20 ml/min/m²) than in adults (120 ml/ min/m²), rendering them unable to excrete large amount of toxins.

• Lower urinary concentration capacity (up to 600 mOsm/ kg) than in adults (up to 1200 mOsm/kg), with inability to tolerate excessive fluid loss.

• Lower urinary acidification capacity (not lt;5.5) than in adults, with consequent susceptibility for acidosis.

• Limited Tm for glucose, phosphates, bicarbonates, amino acids, drugs and other metabolites, increasing the risk of corresponding abnormalities.

Most of these functions mature by 3-6 months of age. Consideration of these limitations is of paramount importance in young infants during fluid and electrolyte correction as well as drug therapy.

21.2